Pyrimidylalkylthio benzimidale compounds, pharmaceutical compositions and use

Abstract

This invention relates to 2- and 4-pyrimidinylmethylsulphinyl(and thio)benzimidazoles in which the pyrimidyl group is substituted by an optionally substituted amino group. These compounds inhibit exogenously and endogenously stimulated gastric acid secretion.

What is claimed is: 
     
       1. A compound of structure (I) ##STR11## in which, R 1  to R 4  are the same or different and are each hydrogen, C 1-6  alkyl, halogen, trifluoromethyl, C 1-6  alkoxy, C 1-6  alkanoyl or C 1-6  alkoxycarbonyl, RCF 2  O, an ethoxy group substituted by 3 to 5 fluorine atoms n is 0 or 1;   R 5  and R 6  are the same or different and are each hydrogen, C 1-6  alkyl or C 3-6  cycloalkyl, or R 5  and R 6  together with the nitrogen atom to which they are attached form an azetidino, pyrrolidino, piperidino, piperazino, N--C 1-4  alkylpiperazino or morpholino group; and   one of X and Y is a nitrogen atom, and the other is a group CR 7  where R 7  is hydrogen, C 1-4  alkyl or NH 2 ,   or a pharmaceutically acceptable salt thereof.   
     
     
       2. A compound as claimed in claim 1 in which n is 1. 
     
     
       3. A compound as claimed in claim 1 or claim 2 in which R 5  and R 6  together with the nitrogen claim to which they are attached form a pyrrolidino, piperidino, piperazino, NC 1-4  alkyl piperazino, or morpholino group. 
     
     
       4. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-piperidino-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       5. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-morpholino-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       6. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-pyrrolidino-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole   
     
     
       7. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-dimethylamino-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       8. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-piperidino-5-methyl-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       9. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-piperidino-5-amino-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       10. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-dimethylamino-5-methyl-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       11. A compound as claimed in claim 1 which is: 5-methoxy-2-(4-dimethylamino-5-amino-2-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       12. A compound as claimed in claim 1 which is: 5-methoxy-2-(5-methyl-6-piperidino-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       13. A compound as claimed in claim 1 which is: 5-methoxy-2-(5-methyl-6-pyrrolidino-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       14. A compound as claimed in claim 1 which is: 5-methoxy-2-(5-methyl-6-morpholino-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       15. A compound as claimed in claim 1 which is: 5-methoxy-2-(5-methyl-6-dimethylamino-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       16. A compound as claimed in claim 1 which is: 5-methoxy-2-(6-piperidino-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       17. A compound as claimed in claim 1 which is: 5-methoxy-2-(6-pyrrolidino-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       18. A compound as claimed in claim 1 which is: 5-methoxy-2-(6-dimethylamino)-4-pyrimidinylmethylsulphinyl)-(1H)-benzimidazole.   
     
     
       19. A pharmaceutical composition comprising a compound as claimed in claim 1 in association with a pharmaceutically acceptable carrier. 
     
     
       20. A pharmaceutical composition comprising a compound as claimed in claim 2, in association with a pharmaceutically acceptable carrier. 
     
     
       21. A pharmaceutical composition as claimed in claim 20, in a form suitable for oral administration. 
     
     
       22. A pharmaceutical composition as claimed in claim 21, provided with an enteric coating. 
     
     
       23. A pharmaceutical composition as claimed in claim 19 in a form suitable for intravenous administration. 
     
     
       24. A method of inhibiting gastric acid secretion which comprises administering to a mammal in need thereof an effective amount of a compound as claimed in claim 1. 
     
     
       25. A method of treatment of gastrointerstinal diseases and other conditions caused of exacerbated by gastric acidity which comprises administering to a mammal in need thereof an effective amount of a compound as claimed in claim 1.